The invention relates to a hydrogel contact lens of high oxygen permeability, to a polymer material suitable for this purpose and to the use of the latter for producing such lenses.
On its inner side, the natural cornea of the eye has a layer of endothelial cells, which are supplied through the cornea with oxygen from the surrounding air. In order to make this possible, the cornea must therefore have a high oxygen permeability. However, permanent exposure of the cornea to the surrounding air would cause the cornea to dry out. In order to avoid this, the cornea, by blinking of the eye, is permanently wetted with a liquid, which is referred to as tears, and contains proteins, lipoproteins, lipids and mucins in solution. Because this liquid is constantly replenished and evaporates on the surface of the eyes, the materials dissolved in the tear liquid would have to be deposited on the cornea, making it cloudy. So that this does not happen, nature has developed a protective mechanism for which, however, there is not yet a complete explanation.
There is therefore a need for a contact lens which has a high oxygen permeability and a good compatibility and which imitates the properties of the cornea.
The water content of the cornea usually is about 65% to 75% by weight. The cornea itself has an exceptionally high water-retention capability. By these means, an excessive decrease in the moisture content of the cornea surface is avoided, even in dry air, such as cold, polar air, and in air-conditioned spaces, such as aircraft, in which water evaporation is particularly strong. This high water-retention capability also prevents the concentration of the tear liquid increasing to such an extent that the materials dissolved in the liquid crystallize out.
In this connection, it is known that sulfo compounds, especially keratan sulfates and chondroitin sulfates, play a role in the water-retention capability of the natural cornea.
It is furthermore known that, in nature, the deposition of the above-mentioned substances on the surface of the cornea is avoided by a betaine structure within the collagen. Moreover, the collagen of the cornea contains glycine, proline, glutamine, alanine, arginine, asparagines, lysine, leucine, serine, isoleucine, etc. as amino acids.
The U.S. Pat. No. 5,311,223 discloses a hydrogel contact lens, the polymer composition of which consists of a reaction product of hydrophilic methacrylamide as well as an acrylic monomer, which in a preferred embodiment contains a zwitterionic monomer, such as a sulfobetaine, for example, N-(3-sulfopropyl)-N-methacryloxyethyl-N,N-dimethylammonium betaine (SPE), in order to improve the water-retention capability. Moreover, U.S. Pat. No. 4,663,409 discloses that the water-retention capability is improved by polymerizing amino acid monomers into the matrix of a hydrogel contact lens. In many cases, however, the water-retention capability is still not yet satisfactory.
The refractive index is a further, important property of hydrogel contact lenses. The natural cornea has a refractive index of 1.37 and the whole lens of the eye has an overall refractive index of 1.42. The refractive index of the contact lens should therefore approximate that of the cornea, without, however, reducing its water-retention capability.
It is therefore an object of the invention to provide a hydrogel contact lens which exhibits exceptionally high oxygen permeability and a water-retention capability and refractive index which approximate that of the natural cornea.
Pursuant to the invention, this objective is accomplished by a hydrogel contact lens, the base or basic material of which contains monomers, which are modified with amino acids, and zwitterionic monomers, which are modified with betaine. Moreover, the modified monomers preferably are polymerized randomly distributed in the basic material.
Surprisingly, it was found pursuant to the invention that not only does this copolymer have a particularly pronounced water retention capability, but also that a refractive index can be set with it which comes very close to that of the natural cornea of 1.37.
The water content also corresponds to that of the natural cornea. In the swollen state, the contact lens material contains 55% to 60% water. The water content can be adjusted relatively accurately by an appropriate use of the betaines or amino acids, so that lenses with a higher or somewhat lower water content and, with that, also different swelling capabilities, can be obtained, as desired.
Pursuant to the invention, the amino acids are polymerized directly into the polymer. For this purpose, they are preferably tied into a monomer, which can be linked to the polymer chain. Pursuant to the invention, preferred monomers are those which can be co-polymerized directly with the basic lens material, that is, incorporated directly into the polymer chain. Pursuant to the invention, xcex1, xcex2 unsaturated carbonyl compounds (carbonyl modified), are particularly preferred. In this way, the modified amino acids, used for the copolymerization, are obtained. The betaimes, which are used pursuant to the invention are also co-polymerized in this manner in the polymer matrix.
Preferably, the amino acids are those which occur in the natural collagen of the cornea, such as those named above, or a mixture thereof, glycine being preferred. Basically, all natural or synthetic amino acids, such as xcex2-alanine, xcex3-aminobutyric acid, xcfx89-aminocapronic acid, xcfx89-aminododecanoic acid, xcex2-cyanalanine, xcex5-methylhistidine, canavanine, djencolic acid, 1-azaserine, xcex3-methyleneglutamic acid, N-methyltyrosine, glycine, alanine, serine, cystine, cysteine, lanthoinine, phenylalanine, tyrosine, diiodotyrosine, tryptophane, histidine, aminobutyric acid, methionine, valine, norvaline, leucine, isoleucine, norleucine, arginine, ornithine, lysine, aspartic acid, glutamic acid, threonine, hydroxyglutamic acid, proline, hydroxyproline, asparagine, glutamine, desmosine, isodesmosine and 5-hydroxylysine can be used.
Acrylic acid, crotonic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid and their functional derivatives, such as acid chlorides, anhydrides, amides and esters are xcex1,xcex2-unsaturated carbonyl modifiers for the modified amino acids.
Preferably, the amino acid, polymerized into the basic material of the contact lens, is present as methacryloyl amino acid. Preferably, the amino acid monomer and the betaine monomer are co polymerized with a main chain and/or a side chain of the matrix material.
The percentage of amino acid in the polymer, preferred with respect to the water-retention capability and the refractive index, is 0.5% to 25% by weight, preferably 0.5% to 10% by weight and particularly about 3% by weight.
The betaine, polymerized in the matrix, preferably is present as sulfobetaine, especially as N-(3-sulfopropyl)-N-methacrylxoyethyl-N,N-dimethylammonium betaine (SPE) and/or as carboxybetaine, which forms a block-free copolymer in the basic material.
The percentage of betaine in the polymer, preferred with respect to the water retention capability and the refractive index, is 0.5% to 22% by weight, preferably 0.5% to 10% by weight and especially about 3% by weight.
All transparent polymers are suitable as basic material for the inventive contact lens. Appropriate polymers are, for example, acrylates and/or polyvinyl polymers, especially polyvinylpyrrolidone.
Hydroxyethyl methacrylate (HEMA) and/or hydroxypropyl methacrylate (HPMA), as well as vinylpyrrolidone (VP) or a mixture thereof are particularly preferred basic materials for the contact lens. Acrylamide derivatives, preferably dimethyl acrylamide derivatives, can also be used as the basic material.
Preferably, the percentage of base material in the polymer is 53% to 99% by weight, especially 80% to 99% by weight and particularly about 94% by weight.
The refractive index of the contact lens material does not deviate by more than 10% and preferably not by more 4% from 1.37, that of the natural cornea and, in particular, ranges from 1.370 to 1.441, depending on the mixing ratio and on the amino acid monomers and betaine monomers selected. Preferably, these values are attained in the at least partly and especially in the fully swollen state.
The refractive index of the contact lens material is essentially determined by the main monomer or monomers. Moreover, the refractive index of the especially preferred HEMA polymer in the clean state is 1.442. By co-polymerizing amino acids and/or betaine derivatives into the polymer, the refractive index can be adjusted finely to values between 1.370 and 1.441. In this connection, it should be noted that an increase in the concentration of the amino acid or the betaine derivatives in the polymers leads to a decrease in the refractive index. At the same time, the water content of the polymer is increased. As a result, the refractive index approaches more or less that of pure water of 1.333.
In the swollen state, the inventive contact lens contains more than 50% by weight and preferably 55% to 60% of water.
With the above-described inventive contact lens material, oxygen permeabilities especially with a DK values of  greater than 8xc3x9710xe2x88x9211, preferably of  greater than 15xc3x9710xe2x88x9211 and particularly of about 23xc3x9710xe2x88x9211 can be attained.
According to a further aspect of the invention, a method is provided for the preparation of a polymer material, which is suitable for hydrogel contact lenses and characterized by the steps of mixing methacrylate monomers with monomers modified with amino acids and with monomers modified with betaines and polymerizing this material with a starter and a cross linking agent, particularly by free radical polymerization.
Preferred starters are azo compounds and peroxy compounds and/or photochemical reaction starters. Further suitable starters are peroxides, azo compounds, UV radiation, redox systems and similar starters. Examples of free radical starters which are suitable here, are bis-(isopropyl)-peroxydicarbonate, 2,2xe2x80x2-azobis-(isobutyronitrile), acetyl peroxide, benzoin methyl ether, lauroyl peroxide, decanoyl peroxide, benzoyl peroxide, 2,2xe2x80x2-azobis(2,4-dimethylvaleronitrile), t-butyl peroctoate, phthalyl peroxide, cumene hydroperoxide, diethoxyacetophenone and t-butyl peroxypivalate.
Preferably, the cross linking agent is present in an amount of 0.01% to 3% by weight, especially 0.5% to 2% by weight and particularly 0.1% to 5% by weight. The following are suitable cross linking agents: polyfunctional derivatives of different xcex1,xcex2 unsaturated acids, such acrylic acid, methacrylic acid, crotonic acid, itaconic acid, maleic acid and fumaric acid, acrylamide, methacrylamide and multivinyl-substituted benzenes. Especially suitable are, for example, ethylene glycol diacrylate or dimethyacrylate, diethylene glycol diacrylate or dimethyacrylate, tetraethylene glycol diacrylate or dimethyacrylate, polyethylene glycol diacrylate or dimethyacrylate, trimethylolpropane triacrylate or trimethacrylate, bisphenol A diacrylate or dimethyacrylate, ethoxylated bisphenol A diacrylate or dimethyacrylate, pentaerythritol triacrylate and tetracrylate or methacrylate, tetramethylene diacrylate or dimethyacrylate, methylene bisacrylamide or bismethcrylamide, dimethylene bisacrylamide or bismethacrylamide, N,Nxe2x80x2-dihydroxyethylene bisacrylamide or bismethacrylamide, hexamethylene bisacrylamide or bismethacrylamide, decamethylene bisacrylamide or bismethacrylamide, divinylbenzene, vinyl methacrylate and allyl methacrylate. Furthermore, cross linking agents based on siloxanes, as well as resonance-free cyclic di(alkylene tertiary amine) compounds, such as N,Nxe2x80x2-divinyl ethylene urea, or also divinyl or polyvinyl ethers and divalent or polyvalent alcohols, such as ethylene glycol divinyl ether, come into consideration.
The contact lens can be produced individually as a cast lens, with a polymerization time of less than 1 hour and preferably of less than 30 minutes. Preferably, 0.2% to 0.5% by weight of reaction starter is used.
According to a further possibility, the mixture is polymerized first into a block-shaped, preferably rod-shaped material for a prolonged period of about 1 to 3 days under a controlled temperature. The individual lenses are then produced mechanically from this block material, for example, on a lathe. In this case, preferably 0.05% to 0.2% by weight of reaction starter is used.
In a further inventive embodiment, up to 20% by weight of glycerin are added for the polymerization.